Peptide-Polymer Engineering Dentin/Adhesive Interfacial Bond Integrity

肽-聚合物工程牙本质/粘合剂界面结合完整性

• 批准号: 9754105
• 负责人: Paulette Spencer
• 金额: $ 14.33万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-07 至 2020-08-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9754105
• 关键词: Acetylesterase; Acids; Acute; Adhesives; Affect; Amalgam; Bacteria; Biodegradation; Chemicals; Chemistry; Chronic; Clinical; Clinical Data; Clinical Research; Collagen; Dental Cavity Preparation; Dental Enamel; Dental caries; Dentin; Deterioration; Disinfection; Engineering; Environment; Enzymes; Esters; Event; Failure; Fatigue; Feedback; Formulation; Gingiva; Goals; Hybrids; Hydrolysis; In Situ; Infiltration; Kinetics; Lead; Liquid substance; Matrix Metalloproteinases; Mechanics; Methacrylates; Minerals; Modeling; Oral; Patients; Peptides; Plant Resins; Polymers; Porosity; Property; Recurrence; Replacement Therapy; Residual state; Resistance; Salivary; Site; Streptococcus mutans; Stress; Structure; Techniques; Testing; Time; Tooth structure; Viscosity; Water; analog; base; clinically relevant; composite restoration; covalent bond; demineralization; esterase; high risk; improved; in vivo; interfacial; mechanical properties; novel; pathogen; predictive modeling; public health relevance; remineralization; restoration; restorative dentistry; seal

 DESCRIPTION (provided by applicant): In 2006, 173 million composite and amalgam restorations were placed in the U.S. and clinical data suggest that >100 million were replacements. Since composites fail at a rate double that of amalgam, the emphasis on replacement therapy will increase with the elimination of amalgam. Recurrent decay is the primary reason for failure and 80-90% of recurrent decay is located at the gingival margin of the composite restoration. At this margin, the adhesive and its bond with dentin is the barrier between the restored tooth and the oral environment. In vivo degradation of the adhesive bond follows a cascade of events; these events are provoked by matrix metalloproteinases (MMPs) that degrade water-rich collagen that is not shielded by mineral or resin; acids and esterases released by the residual bacteria that contaminate the cavity; esterases and oral fluids that degrade the adhesive. Establishing and maintaining the interfacial integrity of the adhesive/dentin (a/d) bond has been a critical roadblock to durable composite restorations. Our approach involves a threefold strategy that: (i) exploits peptide engineering to disinfect the cavity and remineralize deficient dentin - the peptides are localized at the substrate by anchoring to the adhesive and dentin; (ii) engineers resins to resist chemical and enzymatic hydrolysis; and (iii) employs iterative feedback between synthesis, characterization and modeling to predict properties and promote targeted optimization of the adhesive. Combining bio- enabled techniques with synthesis of novel polymers, the overall hypothesis is that an adhesive formulation that achieves a durable, integrated a/d interfacial bond will provide an enhanced barrier to cariogenesis as compared to state-of-the-art dentin adhesives. Our goal is to show how altering the material chemistry and anchoring targeted peptides will lead to predictable changes in properties (resist chemical and enzymatic hydrolysis, disinfect the cavity, remineralize the dentin) and to optimize features for in situ a/d bond formation and interfacial integrity based on kinetics, fatigue, multi-scale structure/property characterization and predictiv modeling. The specific Aims are: 1) to synthesize the most promising formulation that provides disinfection and remineralization using peptide engineering and iterative experimental/computational approaches; 2) to determine the hydrolytic and enzymatic resistance of the versatile resin matrices; 3) to test the bio-physicochemical and mechanical properties of the new adhesive at the interface between composite and caries-free and caries-affected dentin.

 描述（由申请人提供）：2006年，美国共植入了1.73亿例复合材料和汞合金置换术，临床数据表明其中超过1亿例为置换术。由于复合材料的失效率是汞合金的两倍，因此随着汞合金的淘汰，对替代疗法的重视将增加。复发性龋坏是修复失败的主要原因，80-90%的复发性龋坏位于复合修复体的龈缘。在这个边缘，粘合剂及其与牙本质的粘合是修复牙齿和口腔环境之间的屏障。粘合剂结合的体内降解遵循一系列事件;这些事件由基质金属蛋白酶（MMP）引起，其降解未被矿物质或树脂屏蔽的富含水的胶原蛋白;污染腔体的残留细菌释放的酸和酯酶;降解粘合剂的酯酶和口腔液。建立和保持粘接剂/牙本质（a/d）粘接的界面完整性一直是持久复合材料修复的关键障碍。我们的方法涉及三重策略，即：（i）利用肽工程来消毒腔体并使缺陷牙本质再生-肽通过锚定到粘合剂和牙本质而定位在基底处;（ii）设计树脂以抵抗化学和酶水解;以及（iii）在合成，表征和建模之间采用迭代反馈来预测特性并促进粘合剂的目标优化。将生物激活技术与新型聚合物的合成相结合，总体假设是，与最先进的牙本质粘合剂相比，实现持久的、一体化的a/d界面结合的粘合剂制剂将提供增强的龋齿发生屏障。我们的目标是展示如何改变材料化学和锚定靶向肽将导致可预测的性质变化（抵抗化学和酶水解，消毒腔，使牙本质软化），并基于动力学，疲劳，多尺度结构/性质表征和预测建模优化原位a/d键形成和界面完整性的特征。具体目标是：1）使用肽工程和迭代实验/计算方法合成提供消毒和再矿化的最有前途的制剂; 2）确定通用树脂基质的耐水解性和耐酶性; 3）测试复合材料与无龋和龋影响牙本质之间界面处的新粘合剂的生物物理化学和机械性能。